Projects per year
Context: Cortisol has a distinct circadian rhythm regulated by the brain's central pacemaker. Loss of this rhythm is associated with metabolic abnormalities, fatigue and poor quality of life. Conventional glucocorticoid replacement cannot replicate this rhythm. Objectives: To define key variables of physiological cortisol rhythm and by pharmacokinetic modelling test whether modified-release hydrocortisone (MR-HC) can provide circadian cortisol profiles. Setting: Clinical Research Facility. Design and Methods: Using data from a cross-sectional study in healthy reference subjects (n=33) we defined parameters for the cortisol rhythm. We then tested MR-HC against immediate-release (IR-HC) in healthy volunteers (n=28) in an open-label, randomised, single-dose, crossover study. We compared profiles to physiological cortisol levels, and modelled an optimal treatment regimen. Results: The key variables in the physiological cortisol profile included: peak 15.5mcg/dL (95% reference range 11.7-20.6), acrophase 0832h (95%CI 0759h-0905h), nadir
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- 1 Finished
1/08/04 → 31/10/09
Project: Research Councils